title: A biosensor-based characterization of the affinity maturation of the immune response against interferon-beta and correlations with neutralizing antibodies in treated multiple sclerosis patients.
abstract: The study of antibodies against Interferon-beta (IFN-beta) in treated multiple sclerosis (MS) patients has focused primarily on detection and quantification, with no single method of detection providing a comprehensive characterization. We assessed serial samples of 18 MS patients, treated with IFN-beta for between 66 and 198 months, to characterize the affinity maturation of these antibodies using a biosensor-based approach (Biacore). Biacore utilizes the principles of surface plasmon resonance (SPR) with data from the dissociation phase of the antigen-antibody reaction being inversely proportional to relative antibody affinity. In patients with neutralizing antibodies (NAbs+), mean antibody dissociation rates decreased from 0.00118 +/- 0.00030 s(-1) at month 6 to 0.00021 +/- 0.00008 s(-1) at month 36, followed by a slight increase to 0.00027 +/- 0.00003 s(-1) at month 60. In NAb- patients, mean antibody dissociation rates decreased only very slightly from 0.00130 +/- 0.00025 s(-1) to 0.00105 +/- 0.00020 s(-1) at month 18, followed by a gradual increase to 0.00243 +/- 0.00099 s(-1) at month 60. Our study shows little improvement in antibody affinity in NAb- patients, in contrast to a marked increase in antibody affinity over time in NAb+ patients with a significant correlation between NAb titers and relative antibody dissociation rates (Spearman's correlation, R(2) = -0.374, p < 0.001). The evaluation of relative antibody affinities will contribute to a thorough understanding of the anti-IFN-beta antibody response.
authors.affiliation: NeuroImmunology Labs, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. ebgibbs@interchange.ubc.ca
authors.forename: Ebrima
authors.initials: E
authors.lastname: Gibbs
authors.forename: Joel
authors.initials: J
authors.lastname: Oger
mesh_terms: D000906:Antibodies / Q000097:blood*; D000915:Antibody Affinity / Q000276:immunology; D000937:Antigen-Antibody Reactions / Q000276:immunology; D015374:Biosensing Techniques; D006801:Humans; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D009500:Neutralization Tests
chemical_list: D000906:Antibodies; D016899:Interferon-beta